TICK RESOURCES CORE Abstract: The overarching goal of the Tick Resources Core within this P01 application is to provide support to all three research projects and share reagents, materials and new technologies with the scientific community. Requests from the community will be handled through the Biodefense and Emerging Infections Research Resources Repository (BEI) website (www.beiresources.org). BEI was established by the National Institute of Allergy and Infectious Diseases and has been managed under contract by the American Type Culture Collection for fifteen years. Dr. Ulrike Munderloh, a Professor at the University of Minnesota, will be the director of this technical core and is ideally suited to manage the facility. First, she has been a pioneer in the field of tick-pathogen interactions by developing and refining techniques for mutagenesis, plasmid-based complementation, and functional genomics for rickettsial agents in addition to inventing a membrane feeder system for ticks. Second, her laboratory has contributed to 22 out of 30 Rickettsiales species for sequencing in the ?Rickettsiales Genomes? project, and supplied 10 of the 14 isolates deposited in BEI. Third, Dr. Munderloh has an outstanding record of distributing tick cell lines and microbial isolates to the scientific community. Aim#1 of the Tick Resources Core will provide currently available tick-vector-based tools to support the research for all three research projects within this P01 application. Aim#2 of the Tick Resources Core will develop novel cell lines suitable for analyses of immune pathways that are activated or repressed in response to pathogens, symbionts and selected microbiota. This will be achieved through RNA interference, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9), reporter tags and overexpression assays. Model organisms have a myriad of tools that facilitate the study of pathogen-arthropod interactions. They also provide critical insights to the field of entomology, microbiology and immunology. However, we present strong evidence in this P01 application that Ixodes scapularis ticks seem to be built on entirely different principles that govern microbial pathogenesis and immunity. Therefore, a strong Tick Resources Core is of utmost importance to support all three Projects within this P01 application. By providing existing I. scapularis-based tools and developing novel technologies to investigators, the Tick Resources Core will contribute to uncover novel paradigms in I. scapularis-microbial interactions. This scientific knowledge has potential implications for basic and translational science.